Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is work­ing on putting to­geth­er a late-stage study for its mon­o­clon­al an­ti­body Gazy­va in pa­tients with se­vere kid­ney dis­ease as­so­ci­at­ed with lu­pus af­ter a com­bi­na­tion ap­proach helped pa­tients in a mid-stage study.

The 125-pa­tient NO­BIL­I­TY tri­al eval­u­at­ed Gazy­va, com­bined with stan­dard-of-care treat­ment my­cophe­no­late mofetil or my­cophe­no­lic acid and cor­ti­cos­teroids, ver­sus stan­dard treat­ment alone. The com­bo met the main goal of in­duc­ing a sta­tis­ti­cal­ly su­pe­ri­or com­plete re­nal re­sponse (CRR) of 40% at week 76, ver­sus 18% in pa­tients giv­en stan­dard treat­ment, Roche said.

The drug, which is be­ing test­ed alone and in com­bi­na­tion with oth­er ther­a­pies across a range of blood can­cers, is en­gi­neered to at­tach to CD20, a pro­tein found on cer­tain B-cells. It is thought to work by at­tack­ing tar­get­ed cells both di­rect­ly and in tan­dem with the body’s im­mune sys­tem. Gazy­va, which is al­ready ap­proved for use in cer­tain can­cers, gen­er­at­ed near­ly $342 mil­lion in the first nine months of 2019 and has been grant­ed break­through ther­a­py sta­tus for lu­pus nephri­tis.

On the safe­ty side, wor­ries that pro­found B cell de­ple­tion would ham­per the drug’s pro­file were abat­ed af­ter the Gazy­va arm reg­is­tered a se­ri­ous ad­verse event rate of 24%, while pa­tients on the stan­dard care arm saw a rate of 29%. In terms of se­ri­ous in­fec­tions, the rate was 9% on the Gazy­va arm and 18% in the stan­dard group.

Richard Fu­rie North­well Health

“The strat­e­gy to tar­get B cells (an­ti­body-pro­duc­ing white blood cells re­spon­si­ble for pro­duc­ing lu­pus an­ti­bod­ies) in sys­temic lu­pus and lu­pus nephri­tis was bi­o­log­i­cal­ly sound. How­ev­er, two stud­ies did not achieve their re­spec­tive end­points,” said Richard Fu­rie, chief of rheuma­tol­ogy at North­well Health in a state­ment.

“Af­ter a hia­tus of sev­er­al years, a de­ci­sion was made to move for­ward with a third-gen­er­a­tion B cell-de­plet­ing an­ti­body…The hy­poth­e­sis was that a more po­tent an­ti­body might re­sult in greater de­ple­tion of B cells and that this may yield a greater clin­i­cal re­sponse in those pa­tients with ac­tive kid­ney dis­ease.”

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been one FDA ap­proval. In re­cent years, the field has re­sem­bled a grave­yard. Last Oc­to­ber, UCB and Bio­gen’s $BI­IB an­ti-CD40L drug failed in a late-stage study, months af­ter Xen­cor $XN­CR and Sanofi’s $SNY Abl­ynx al­so con­ced­ed de­feat in their pro­grams. In Au­gust, how­ev­er, As­traZeneca of­fered a glim­mer of hope af­ter its drug, an­i­frol­um­ab, cleared a Phase III study.

The on­ly bi­o­log­ic so far to win ap­proval for lu­pus is GSK’s $GSK Benlysta — which was cleared for adult use in 2011 and for rare cas­es of child­hood lu­pus this year. (GSK is in the midst of test­ing Benlysta in com­bi­na­tion with Roche’s rit­ux­imab in the hope the com­bi­na­tion will have a more po­tent ef­fect on the dis­ease ver­sus Benlysta monother­a­py.)

The sys­temic au­toim­mune dis­ease, in which the body’s im­mune sys­tem launch­es an at­tack on its own tis­sues and or­gans, af­fects about 1.5 mil­lion Amer­i­cans, ac­cord­ing to The Lu­pus Foun­da­tion of Amer­i­ca. Lu­pus nephri­tis oc­curs when the dis­ease rav­ages the kid­neys, trig­ger­ing in­flam­ma­tion that could lead to blood and/or pro­tein in the urine, high blood pres­sure, poor kid­ney func­tion, or kid­ney fail­ure. Rough­ly 60% of lu­pus pa­tients de­vel­op lu­pus nephri­tis and 1 in 4 progress to end-stage re­nal dis­ease.

So­cial im­age: Roche

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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